Fatigue is a highly prevalent and debilitating symptom of HIV-infection, associated with a high degree of psychological and functional morbidity. Recent reports estimate that fatigue is a distressing symptom in at least 40-50% of AIDS patients. During the course of conducting a study of the impact of pain on quality of life, we discovered that fatigue was among the most prevalent and distressing symptoms experienced by ambulatory AIDS patients, even more prevalent than pain. In our cohort of 360 AIDS patients, 72% experienced "persistent fatigue (feeling tired all the time) for at least two weeks." Furthermore, our preliminary analyses demonstrate a significant association between fatigue and depression, hopelessness and overall psychological distress. Interventions for fatigue related to medical illnesses have included non-pharmacologic (exercise, energy conservation) and pharmacologic (corticosteroids, psychostimulants) therapies, however there have been few controlled studies. Psychostimulants have been demonstrated to be useful in the management of depressive symptoms, as well as, cognitive slowing (related to dementia) in cancer and AIDS patients. Thus, their potential as adjuncts to the management of fatigue is of interest to mental health professionals, particularly as it pertains to the interface between physical and psychological symptoms in the medically ill. Treatment of fatigue with psychostimulant medications (methylphenidate, amphetamine, pemoline) has been studied, to a limited degree, in cancer and multiple sclerosis, but has not yet been studied in HIV. This project's overall aim is to study the efficacy of psychostimulant drugs in the treatment of fatigue in HIV- infected patients. We will compare the frequency and severity of treatment emergent adverse side effects, as well as, examine the impact of psychostimulant treatment for fatigue on depression and overall quality of life. Specifically, we will be conducting a randomized, double-blind, placebo-controlled, parallel design trial, evaluating the relative benefits and risks of two psychostimulant medications (methylphenidate, pemoline), in the treatment of fatigue in HIV-infected patients. This study will be the first controlled evaluation of a pharmacologic intervention for fatigue in HIV-infected patients that utilizes novel psychotropic agents (psychostimulants), and assesses outcome with validated measures of fatigue (the Piper Fatigue Scale), side-effects, psychological distress and overall quality of life.